The work relates to our understanding of the biochemical events associated with the normal function of the thyroid and to pathological conditions of the thyroid, such as Graves' disease. Iodide transport mechanisms have been characterized in detail and include a sodium-dependent iodide uptake process and an independent efflux pathway. A variety of pharmacological agents, including adrenergic drugs as well as thyrotropin (TSH), were shown to have specific effects on iodide influx or efflux. Iodide transport is dependent on protein synthesis induced by TSH or cyclic AMP. A profile of the appearance of proteins induced by TSH was described. Studies have been initiated to identify several proteins involved in thyroidal function, e.g., iodide "carrier" protein, thyroglobulin, TSH, and Fc binding proteins. Iodide flux stimulated by TSH and norepinephrine was dependent on calcium and not mediated by cAMP, TSH- (and norepinephrine-) stimulated ion fluxes have been linked to the breakdown of polyphosphoinositides, lipids implicated in calcium release from the plasma membrane. These agents also stimulate phosphatidic acid and phosphatidylinositol turnover. The work continues to support the hypothesis that alterations in ion fluxes are important early events as well as primary actions of hormones, toxins, and pharmacological agents.